Game plan Lecture Vaccinations ELISAs Lab Complete Staph, Strep and Enteric Unknowns Begin Major Unknown

Immunological applications: vaccines Table 18.3 Attenuated whole-agent vaccines- weakened microbes (measles, mumps, rubella, chickenpox…) Inactivated (killed) whole-agent vaccines- killed microbes (polio, rabies, pertussis) Toxoids- inactivated toxins (tetanus, diptheria, pertussis) Subunit vaccines- partial antigenic fragments of microbes (hepatitis B) Conjugated vaccines- polysaccharides combined with proteins (H. influenza b)

Vaccine schedule Table 18.3

Why not vaccinate? -Complacency about disease -Benefits of vaccination not immediately evident (adverse reactions are immediate) -Media’s biased role -Need to link tragic events (eg. autism) with cause -Philosophical beliefs based on above -Vaccines don’t work. -Why vaccinate when the disease is so rare? -Vaccines cause secondary disease.

Complacency/ benefits example: smallpox success story -Caused by variola virus (major and minor) -First disease for which immunity was artificially induced -Last US case in 1948; last case worldwide in 1977 in Somalia -Further information: Source: Centers for Disease Control and Prevention

Adverse reactions- these can be immediate and obvious IPV or Salk polio vaccine induced 260 cases polio, resulted in 10 deaths (not fully inactivated). Current Salk vaccine is inactivated Rotavirus vaccine and intussesception (bowel obstruction) 1 in 10,000 to 15,000 cases – OPV/ Sabin vaccine causes paralysis in 1/ 6.2 million

Media’s role: inaccurate reporting Case study:1000 students at school 995 received MMR vaccine all exposed to 1 student with measles 12 cases of measles resulted 5 were not previously immunized 7 were immunized (less severe cases) MEDIA REPORT: MMR Vaccine Does Not Work!!

Need to link tragedies with cause MMR vaccine and autism data (Summary of information found in “Vaccines and Autism” article) -1998: Wakefield et al. suggest MMR vaccine caused autism in 12 children ISSUES: MMR vaccine/ autism diagnosis occurs at same time Studies of autism in vaccinated vs. unvaccinated not done Claim that autism is consequence of gastrointestinal inflammation caused by vaccine, but GI issues occurred before vaccine in 8 cases RESULT: Paper was retracted by all but one author Paper was retracted by publishing journal

Need to link tragedies with cause Studies by multiple independent groups to determine causal relationship between MMR vaccine and autism (Summary of information found in “Vaccines and Autism” article) -1999: Taylor et al. examines receipt of MMR vaccine and autism (case study of 500 children) RESULTS: % vaccinated children with autism same as those without No difference in age of diagnosis between vaccinated and unvaccinated children Onset of symptoms did not occur within 6 months of MMR vaccine

Need to link tragedies with cause Genetic basis of autism and timing of development of disease -Genetics: Look at percentage of autism in twins. If one has it: Strict definition of autism 60% of monozygotic twin will have it ~0% of dizygotic twin Broad defintion (autistic spectrum disorder) 92% monozygotic twin will have it 10 % of dizygotic twin will have it Bailey, A., et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 25:63-77, Abstract Folstein, S., et al. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 18: , 1977.

Need to link tragedies with cause Genetic basis of autism and timing of development of disease -Timing:Autism symptoms present before 1 year of age (studies done in 1991, 1992, 1993, 1994, 1998) Autism symptoms present before 4 months (studies done in 1998) Adrien, J., et al. Blind ratings of early symptoms of autism based upon family home movies. J Am Acad Child Adolesc Psychiatry Adrien, J., et al. Early symptoms in autism from family home movies: evaluation and comparison between 1st and 2nd year of life using I.B.S.E. scale. Acta Paedopsychiatrica 55:71-75, Adrien, J., et al. Autism and family home movies: preliminary findings. J Autism Devel Disorders 21:43-49,1991. Osterling, J., et al. Early recognition of children with autism: a study of first birthday home videotapes.J Autism Devel Disorders 24: , Mars, A.E., et al. Symptoms of pervasive developmental disorders as observed in prediagnostic home videos of infants and toddlers. J Pediatr 132: , Teitelbaum, P., et al. Movement analysis in infancy may be useful for the early diagnosis of autism. Proc Natl Acad Sci USA 95: , Stromland, K., et al. Autism in thalidomide embropathy: a population study. In Devel Med Child Neurol 36: , Rodier P., et al. Embryological origin for autism: developmental anomalies of the cranial nerve motor nuclei. J Comp Neurol 370: , 1996.

Need to link tragedies with cause WHAT NOW? -Years of research to refute hypothesis and calm fears Link to CDC research page -Exemptions allowed in 19 states- places community at risk -Increase in measles in population due to exemptions for MMR vaccine (was declared eliminated in 2000 from US)

Refusing vaccinations- who suffers? -Measles caused by Rubeola virus -Symptoms: fever, rash, conjunctivitis, pneumonia, blindness, deafness, encephalitis (permanent damage), and/or death -Pre-vaccine: 500,000 cases, 7500 deaths, 28,000 hospitalizations, 1,000 children with chronic disabilities (US ONLY) -Highly contagious: requires > 90% vaccination coverage in population -Currently leading cause of death from a vaccine-preventable disease: ,700 deaths (400 per day, 16 per hour); 134 cases in California since Dec

-San Diego- February unvaccinated child returning from EU -Documented 11 cases (all in unvaccinated children), 8 of whom had PBEs - 3 in children < 12 months -Spread prior to ID of etiological agent (MMWR) -San Diego County school districts have anywhere from 40-70% PBE exemptions on file per district vaccines-look-up-your-school-online/ Refusing vaccinations- who suffers?

Vaccines- the bottom line -Vaccines work! A total 98.8% reduction in vaccine preventable diseases in the US since vaccination schedule was implemented. -Exemptors of vaccines break down herd immunity and increase risk of disease on a population level -Vaccines will never be 100% effective or 100% safe Primary goal of current vaccine research is based on safety and EIDs -It is a personal choice, but be aware that one’s choice affects the rest of the community -Personal vigilence is required to be informed and prevent complacency in public, health organizations, and research/ drug development

Diagnostic applications: Enzyme-Linked Immunosorbent Assay (Direct ELISA) Figure 18.12a

Enzyme-Linked Immunosorbent Assay (Direct vs Indirect ELISA) Figure Overview

New lateral flow (ELISA) technology Immunocard: Detects C. difficile toxins A and B Immunocard: STAT! Detects H. pylori in stool

New lateral flow (ELISA) technology Binax NOW Malaria: Differentiates between P. falciparum and others NOW Flu: Detects influenza A and B